Favourable cardiovascular safety profile for semaglutide
medwireNews: Semaglutide significantly reduces the likelihood of adverse cardiovascular outcomes among patients with Type 2 diabetes at high cardiovascular risk, the SUSTAIN-6 study shows.
SUSTAIN-6 (Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes) involved 3297 high-risk patients, of whom 83% had established cardiovascular disease, including chronic kidney disease.
The noninferiority trial was powered to demonstrate that semaglutide did not increase patients’ risk of cardiovascular outcomes by 1.8-fold or more versus placebo – a margin set by the US Food and Drug Administration.
But the patients had a higher number of events than the researchers had anticipated, giving them the statistical power to show significant benefit with semaglutide. Over a median of 2.1 years, 6.6% of patients taking the glucagon-like peptide 1 (GLP-1) analogue, at doses of 0.5 or 1.0 mg/week, met the primary endpoint of cardiovascular death, nonfatal myocardial infarction (including subclinical) or nonfatal stroke.
This equated to a significant 26% reduction relative to the placebo group, 8.9% of whom met the primary endpoint. The difference was driven by reduced myocardial infarction and stroke rates.
Semaglutide was also associated with a significantly reduced rate of revascularisation and of new or worsening nephropathy, making its safety profile broadly in line with that of other GLP-1 receptor agonists.
However, patients taking semaglutide did have a significantly higher rate of retinopathy complications, at 3.0% versus 1.8% in the placebo group, report Steven Marso (Research Medical Center, Kansas City, Missouri, USA) and study co-authors.
“An association between rapid glucose lowering and worsening of retinopathy has been reported in patients with type 1 diabetes”, the researchers write in The New England Journal of Medicine.
But they add: “The applicability of such an association to our finding is unclear, and a direct effect of semaglutide cannot be ruled out.”
Glycaemic control was better in the semaglutide group than the placebo group, with glycated haemoglobin levels falling from 8.7% at baseline to 7.6% and 7.3% in patients taking the 0.5 mg and 1.0 mg doses, respectively, compared with 8.3% in those taking placebo. Patients taking semaglutide also achieved significant reductions in bodyweight (with both doses) and blood pressure (with the 1.0 mg dose) relative to the placebo group.
“The reductions in glycated hemoglobin, body weight, and systolic blood pressure may all have contributed to the observed reduction in cardiovascular risk with semaglutide”, say the researchers.
medwireNews is an independent medical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2016